The anti-tumoral drug enzastaurin inhibits natural killer cell cytotoxicity via activation of glycogen synthase kinase-3β

Biochemical Pharmacology

Volumn 81, Issue 2, 2011, Pages 251-258

  Ogbomo, Henry ^a   Biru, Tsigereda ^a   Michaelis, Martin ^a   Loeschmann, Nadine ^a   Doerr, Hans Wilhelm ^a   Cinatl Jr , Jindrich ^a  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

Author keywords

Antibody dependent cellular cytotoxicity; Glycogen synthase kinase 3 ; Natural cytotoxicity; NKG2D; Protein kinase C

Indexed keywords

CD16 ANTIGEN; ENZASTAURIN; GAMMA INTERFERON; GLYCOGEN SYNTHASE KINASE 3BETA; NATURAL KILLER CELL RECEPTOR NKG2D; PERFORIN;

ARTICLE; CELL VIABILITY; CYTOKINE PRODUCTION; DOWN REGULATION; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; HUMAN; HUMAN CELL; NATURAL KILLER CELL MEDIATED CYTOTOXICITY; PRIORITY JOURNAL; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION;

ANTINEOPLASTIC AGENTS; CELL LINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME ACTIVATION; GLYCOGEN SYNTHASE KINASE 3; HUMANS; INDOLES; KILLER CELLS, NATURAL; PERFORIN; PHOSPHORYLATION; THIADIAZOLES;

EID: 78650170503     PISSN: 00062952     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bcp.2010.09.026     Document Type: Article

References (67)

1. J.R. Graff, A.M. McNulty, K.R. Hanna, B.W. Konicek, R.L. Lynch, and S.N. Bailey The protein kinase Cbeta-selective inhibitor, Enzastaurin (LY317615. HCl), suppresses signaling through the AKT pathway, induces apoptosis, and suppresses growth of human colon cancer and glioblastoma xenografts Cancer Res 65 2005 7462 7469 (Pubitemid 41161281)
2. B. Glimelius, M. Lahn, S. Gawande, A. Cleverly, C. Darstein, and L. Musib A window of opportunity phase II study of enzastaurin in chemonaive patients with asymptomatic metastatic colorectal cancer Ann Oncol 21 2010 1020 1026
3. M.J. Robertson, B.S. Kahl, J.M. Vose, S. de Vos, M. Laughlin, and P.J. Flynn Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma J Clin Oncol 25 2007 1741 1746 (Pubitemid 46797955)
4. A.T. Ting, R.A. Schoon, R.T. Abraham, and P.J. Leibson Interaction between protein kinase C-dependent and G protein-dependent pathways in the regulation of natural killer cell granule exocytosis J Biol Chem 267 1992 23957 23962 (Pubitemid 23088210)
5. J.D. Bonnema, L.M. Karnitz, R.A. Schoon, R.T. Abraham, and P.J. Leibson Fc receptor stimulation of phosphatidylinositol 3-kinase in natural killer cells is associated with protein kinase C-independent granule release and cell-mediated cytotoxicity J Exp Med 180 1994 1427 1435 (Pubitemid 24289616)
6. A. Kvanta, C. Nordstedt, B. Fredholm, M. Gullberg, and M. Jondal Evidence that protein kinase C activation is essential for killing by IL-2-activated lymphocytes Scand J Immunol 31 1990 103 108 (Pubitemid 20036727)
7. A. Balendran, G.R. Hare, A. Kieloch, M.R. Williams, and D.R. Alessi Further evidence that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms FEBS Lett 484 2000 217 223
8. E. Beurel, and R.S. Jope Glycogen synthase kinase-3 promotes the synergistic action of interferon-gamma on lipopolysaccharide-induced IL-6 production in RAW264.7 cells Cell Signal 21 2009 978 985
9. A. Aoukaty, and R. Tan Role for glycogen synthase kinase-3 in NK cell cytotoxicity and X-linked lymphoproliferative disease J Immunol 174 2005 4551 4558
10. B. Perussia Fc receptors on natural killer cells Curr Top Microbiol Immunol 230 1998 63 88 (Pubitemid 28183718)
11. R. Niwa, S. Hatanaka, E. Shoji-Hosaka, M. Sakurada, Y. Kobayashi, and A. Uehara Enhancement of the antibody-dependent cellular cytotoxicity of low-fucose IgG1 is independent of FcgammaRIIIa functional polymorphism Clin Cancer Res 10 2004 6248 6255 (Pubitemid 39287533)
12. Y.T. Bryceson, M.E. March, H.G. Ljunggren, and E.O. Long Activation, coactivation, and costimulation of resting human natural killer cells Immunol Rev 214 2006 73 91 (Pubitemid 44707903)
13. A. Moretta, E. Marcenaro, S. Parolini, G. Ferlazzo, and L. Moretta NK cells at the interface between innate and adaptive immunity Cell Death Differ 15 2008 226 233
14. E. Vivier, J.A. Nuns, and F. Vély Natural killer cell signaling pathways Science 306 2004 1517 1519 (Pubitemid 39564941)
15. L.L. Lanier Natural killer cell receptor signaling Curr Opin Immunol 15 2003 308 314 (Pubitemid 36645107)
16. J.L. Upshaw, L.N. Arneson, R.A. Schoon, C.J. Dick, D.D. Billadeau, and P.J. Leibson NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells Nat Immunol 7 2006 524 532
17. D.D. Billadeau, J.L. Upshaw, R.A. Schoon, C.J. Dick, and P.J. Leibson NKG2D-DAP10 triggers human NK cell-mediated killing via a Syk-independent regulatory pathway Nat Immunol 4 2003 557 564 (Pubitemid 36701339)
18. D.B. Graham, M. Cella, E. Giurisato, K. Fujikawa, A.V. Miletic, and T. Kloeppel Vav1 controls DAP10-mediated natural cytotoxicity by regulating actin and microtubule dynamics J Immunol 177 2006 2349 2355 (Pubitemid 44200995)
19. E. Giurisato, M. Cella, T. Takai, T. Kurosaki, Y. Feng, and G.D. Longmore Phosphatidylinositol 3-kinase activation is required to form the NKG2D immunological synapse Mol Cell Biol 27 2007 8583 8599
20. I. Tassi, M. Cella, R. Presti, A. Colucci, S. Gilfillan, and D.R. Littman NK cell-activating receptors require PKC-theta for sustained signaling, transcriptional activation, and IFN-gamma secretion Blood 112 2008 4109 4116
21. S. Chiesa, M. Mingueneau, N. Fuseri, B. Malissen, D.H. Raulet, and M. Malissen Multiplicity and plasticity of natural killer cell signaling pathways Blood 107 2006 2364 2372 (Pubitemid 43345556)
22. K. Jiang, B. Zhong, D.L. Gilvary, B.C. Corliss, E. Hong-Geller, and S. Wei Pivotal role of phosphoinositide-3 kinase in regulation of cytotoxicity in natural killer cells Nat Immunol 1 2000 419 425
23. K. Jiang, B. Zhong, D.L. Gilvary, B.C. Corliss, E. Vivier, and E. Hong-Geller Syk regulation of phosphoinositide 3-kinase-dependent NK cell function J Immunol 168 2002 3155 3164 (Pubitemid 34250374)
24. I. Tassi, R. Presti, S. Kim, W.M. Yokoyama, S. Gilfillan, and M. Colonna Phospholipase C-gamma 2 is a critical signaling mediator for murine NK cell activating receptors J Immunol 175 2005 749 754 (Pubitemid 41094955)
25. A. Caraux, N. Kim, S.E. Bell, S. Zompi, T. Ranson, and S. Lesjean-Pottier Phospholipase C-gamma2 is essential for NK cell cytotoxicity and innate immunity to malignant and virally infected cells Blood 107 2006 994 1002 (Pubitemid 43156297)
26. J. Regunathan, Y. Chen, S. Kutlesa, X. Dai, L. Bai, and R. Wen Differential and nonredundant roles of phospholipase Cgamma2 and phospholipase Cgamma1 in the terminal maturation of NK cells J Immunol 177 2006 5365 5376 (Pubitemid 44527609)
27. J.L. Upshaw, R.A. Schoon, C.J. Dick, D.D. Billadeau, and P.J. Leibson The isoforms of phospholipase C-gamma are differentially used by distinct human NK activating receptors J Immunol 175 2005 213 218 (Pubitemid 40884321)
28. M. Cella, K. Fujikawa, I. Tassi, S. Kim, K. Latinis, and S. Nishi Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity J Exp Med 200 2004 817 823 (Pubitemid 39299468)
29. R. Trotta, K.A. Puorro, M. Paroli, L. Azzoni, B. Abebe, and L.C. Eisenlohr Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases J Immunol 161 1998 6648 6656 (Pubitemid 28562206)
30. L.L. Lanier Up on the tightrope: natural killer cell activation and inhibition Nat Immunol 9 2008 495 502 (Pubitemid 351560518)
31. S. Zompi, J.A. Hamerman, K. Ogasawara, E. Schweighoffer, V.L. Tybulewicz, and J.P. Di Santo NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases Nat Immunol 4 2003 565 572 (Pubitemid 36701340)
32. H. Ogbomo, M. Michaelis, D. Klassert, H.W. Doerr, and J. Cinatl Jr. Resistance to cytarabine induces the up-regulation of NKG2D ligands and enhances natural killer cell lysis of leukemic cells Neoplasia 10 2008 1402 1410
33. M. Michaelis, T. Suhan, U.R. Michaelis, K. Beek, F. Rothweiler, and L. Tausch Valproic acid induces extracellular signal-regulated kinase 1/2 activation and inhibits apoptosis in endothelial cells Cell Death Differ 13 2006 446 453
34. R.A. Blaheta, E. Weich, D. Marian, J. Bereiter-Hahn, J. Jones, and D. Jonas Human cytomegalovirus infection alters PC3 prostate carcinoma cell adhesion to endothelial cells and extracellular matrix Neoplasia 8 2006 807 816 (Pubitemid 44564836)
35. M.A. Carducci, L. Musib, M.S. Kies, R. Pili, M. Truong, and J.R. Brahmer Phase I dose escalation and pharmacokinetic study of enzastaurin, an oral protein kinase C beta inhibitor, in patients with advanced cancer J Clin Oncol 24 2006 4092 4099 (Pubitemid 46622284)
36. J. Albanell, J. Codony-Servat, F. Rojo, J.M. Del Campo, S. Sauleda, and J. Anido Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments Cancer Res 61 2001 6500 6510 (Pubitemid 32783257)
37. C. Querfeld, M.A. Rizvi, T.M. Kuzel, J. Guitart, A. Rademaker, and S.S. Sabharwal The selective protein kinase C beta inhibitor enzastaurin induces apoptosis in cutaneous T-cell lymphoma cell lines through the AKT pathway J Invest Dermatol 126 2006 1641 1647
38. K.W. Lee, S.G. Kim, H.P. Kim, E. Kwon, J. You, and H.J. Choi Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric cancer cells Cancer Res 68 2008 1916 1926 (Pubitemid 351416578)
39. K. Guo, Y. Liu, H. Zhou, Z. Dai, J. Zhang, and R. Sun Involvement of protein kinase C beta-extracellular signal-regulating kinase 1/2/p38 mitogen-activated protein kinase-heat shock protein 27 activation in hepatocellular carcinoma cell motility and invasion Cancer Sci 99 2008 486 496 (Pubitemid 351228564)
40. A.S. Moreau, X. Jia, H.T. Ngo, X. Leleu, G. O'Sullivan, and Y. Alsayed Protein kinase C inhibitor enzastaurin induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia Blood 109 2007 4964 4972 (Pubitemid 46827795)
41. L. Chiossone, C. Vitale, F. Cottalasso, S. Moretti, B. Azzarone, and L. Moretta Molecular analysis of the methylprednisolone-mediated inhibition of NK-cell function: evidence for different susceptibility of IL-2- versus IL-15-activated NK cells Blood 109 2007 3767 3775 (Pubitemid 46641727)
42. C.C. Chini, M.D. Boos, C.J. Dick, R.A. Schoon, and P.J. Leibson Regulation of p38 mitogen-activated protein kinase during NK cell activation Eur J Immunol 30 2000 2791 2798
43. P.G. Goekjian, and M.R. Jirousek Protein kinase C inhibitors as novel anticancer drugs Expert Opin Investig Drugs 10 2001 2117 2121
44. J.I. Aguiló, J. Garaude, J. Pardo, M. Villalba, and A. Anel Protein kinase C-theta is required for NK cell activation and in vivo control of tumor progression J Immunol 182 2009 1972 1981
45. T.A. Steele, and Z. Brahmi Inhibition of human natural killer cell activity by the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2- methylpiperazine is an early but post-binding event J Immunol 141 1988 3164 3169
46. K.M. Page, D. Chaudhary, S.J. Goldman, and M.T. Kasaian Natural killer cells from protein kinase C theta-/- mice stimulated with interleukin-12 are deficient in production of interferon-gamma J Leukoc Biol 83 2008 1267 1276 (Pubitemid 351960359)
47. J. Zhang, P.Z. Anastasiadis, Y. Liu, E.A. Thompson, and A.P. Fields Protein kinase C (PKC) betaII induces cell invasion through a Ras/Mek-, PKC iota/Rac 1-dependent signaling pathway J Biol Chem 279 2004 22118 22123 (Pubitemid 38679404)
48. C. Partovian, and M. Simons Regulation of protein kinase B/Akt activity and Ser473 phosphorylation by protein kinase Calpha in endothelial cells Cell Signal 16 2004 951 957 (Pubitemid 38638784)
49. Y. Kawakami, H. Nishimoto, J. Kitaura, M. Maeda-Yamamoto, R.M. Kato, and D.R. Littman Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion J Biol Chem 279 2004 47720 47725 (Pubitemid 39540919)
50. S.E. Aeder, P.M. Martin, J.W. Soh, and I.M. Hussaini PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR signaling pathways Oncogene 23 2004 9062 9069 (Pubitemid 40013073)
51. X. Fang, S. Yu, J.L. Tanyi, Y. Lu, J.R. Woodgett, and G.B. Mills Convergence of multiple signaling cascades at glycogen synthase kinase 3: Edg receptor-mediated phosphorylation and inactivation by lysophosphatidic acid through a protein kinase C-dependent intracellular pathway Mol Cell Biol 22 2002 2099 2110 (Pubitemid 34224618)
52. N. Goode, K. Hughes, J.R. Woodgett, and P.J. Parker Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes J Biol Chem 267 1992 16878 16882
53. D.A. Cross, D.R. Alessi, P. Cohen, M. Andjelkovich, and B.A. Hemmings Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B Nature 378 1995 785 789 (Pubitemid 26004411)
54. R.S. Herbst, Y. Oh, A. Wagle, and M. Lahn Enzastaurin, a protein kinase Cbeta-selective inhibitor, and its potential application as an anticancer agent in lung cancer Clin Cancer Res 13 2007 s4641 s4646
55. K. Podar, M.S. Raab, J. Zhang, D. McMillin, I. Breitkreutz, and Y.T. Tai Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl) Blood 109 2007 1669 1677 (Pubitemid 46239601)
56. C. Holler, J.D. Piñón, U. Denk, C. Heyder, S. Hofbauer, and R. Greil PKCbeta is essential for the development of chronic lymphocytic leukemia in the TCL1 transgenic mouse model: validation of PKCbeta as a therapeutic target in chronic lymphocytic leukemia Blood 113 2009 2791 2794
57. R.S. Jope, and G.V. Johnson The glamour and gloom of glycogen synthase kinase-3 Trends Biochem Sci 29 2004 95 102 (Pubitemid 38186580)
58. B. De Servi, A. Heramni, S. Medunjanin, and D. Mayer Impact of PKCδ onj estrogen receptor localization and activity in breast cancer cells Oncogene 24 2005 4946 4955 (Pubitemid 41129098)
59. T. Gruber, N. Hermann-Kleiter, C. Pfeifhofer-Obermair, C. Lutz-Nicoladoni, N. Thuille, T. Letschka, J. Barsig, M. Baudler, J. Li, B. Metzler, B. Nüsslein-Hildesheim, J. Wagner, M. Leitges, and G. Baier PKC theta cooperates with PKC alpha in alloimmune responses of T cells in vivo Mol Immunol 46 2009 2071 2079
60. N. Isakov, and A. Altman Protein kinase C (theta) in T cell activation Annu Rev Immunol 20 2002 761 794 (Pubitemid 34293439)
61. M. Szamel, U. Ebel, P. Uciechowski, V. Kaever, and K. Resch T cell antigen receptor dependent signalling in human lymphocytes: cholera toxin inhibits interleukin-2 receptor expression but not interleukin-2 synthesis by preventing activation of a protein kinase C isotype. PKC-alpha Biochim Biophys Acta 1356 1997 237 248 (Pubitemid 27190475)
62. J. Gómez, C. Pitton, A. García, A. Martinez de Aragón, A. Silva, and A. Rebollo The zeta isoform of protein kinase C controls interleukin-2-mediated proliferation in a murine T cell line: evidence for an additional role of protein kinase C epsilon and beta Exp Cell Res 218 1995 105 113
63. M. Szamel, A. Appel, R. Schwinzer, and K. Resch Different protein kinase C isoenzymes regulate IL-2 receptor expression or IL-2 synthesis in human lymphocytes stimulated via the TCR J Immunol 160 1998 2207 2214 (Pubitemid 28119900)
64. A.M. Shenoy, and Z. Brahmi Inhibition of the calpain-mediated proteolysis of protein kinase C enhances lytic activity in human NK cells Cell Immunol 138 1991 24 34
65. A.M. Shenoy, R.A. Sidner, and Z. Brahmi Signal transduction in cytotoxic lymphocytes: decreased calcium influx in NK cell inactivated with sensitive target cells Cell Immunol 147 1993 294 301 (Pubitemid 23113928)
66. C.N. Zorn, S. Keck, R.W. Hendriks, M. Leitges, M.A. Freudenberg, and M. Huber Bruton's tyrosine kinase is dispensable for the Toll-like receptor-mediated activation of mast cells Cell Signal 21 2009 79 86
67. H.R. Kim, K.H. Lee, S.J. Park, S.Y. Kim, Y.K. Yang, and J. Tae Anti-cancer activity and mechanistic features of a NK cell activating molecule Cancer Immunol Immunother 58 2009 1691 1700